The goal of this research is to understand how odor information is encoded by the nervous system. Initially, odorants bind to olfactory receptor neurons, which project to glomeruli in the olfactory bulb, the first stage of olfactory information processing. Here, patterns of activity across thousands of receptor neurons are transformed into spatially organized maps of glomerular activation. These maps of receptor input to glomeruli are temporally dynamic, and much of their temporal dynamics are organized around the respiratory cycle. The research in this project will ask how the dynamics of receptor neuron to a glomerulus are translated into firing patterns in the output neurons that project from the olfactory bulb to the cortex (mitral/tufted cells). The projection neurons themselves exhibit complex firing patterns also organized around the respiratory cycle - in fact, it has been hypothesized that the relative timing of firing among them is important for olfactory coding - but the source of these complex dynamics has not yet been identified. This project will test the idea that the temporal dynamics of sensory input evoked during natural odor sampling (i.e., sniffing) is a strong determinant of mitral/tufted cell response patterns. The project will investigate, for the first time, how odor sampling behavior shapes both early olfactory coding at the level of the olfactory bulb and the transformation of receptor inputs into patterns of postsynaptic activity. The experiments proposed here will use optical imaging methods to directly visualize odor-evoked glomerular maps, as well as electrophysiological techniques to record activity from mitral/tufted cells, focusing on responses evoked by naturalistic sampling of odorants. In addition, a simple biophysical computational model of a mitral cell will be implemented and tested to determine its response to naturalistic glomerular input. In addition to testing, for the first time, several longstanding hypotheses about the role of sampling behavior in shaping odor codes, this work will be important in understanding how olfactory information is encoded and processed in the awake, behaving animal. PUBLIC HEALTH RELEVANCE: Understanding the basic principles of olfactory system function can lead to an increased understanding of how the nervous system processes sensory information, including visual, auditory, or touch-related input;such insights could be important in developing artificial sensory organs for humans (for the visually-impaired, for example). Understanding more about mammalian nervous system function also has the potential to lead to improved diagnosis and treatment of diseases of the nervous system.